1. Pharmacologic Treatment Of Asthma 1 د. ميريانا البيضة

2. There are both short-term and long-term therapeutic objectives for every asthmatic patient 2

3. short-term objectives are the control of immediate symptoms 3

4. Long-term objectives are those directed at disease prevention to avoid serious exacerbations 4

5. Reliever Medications Short-Acting inhaled β 2-Agonists(SABA) β 2-Agonists(SABA)Anticholinergics5

6. Controller Medications Controller Medications  Inhaled gluCocorticoSteroids (ICS)  Leukotriene Modifiers (LM)  Theophylline (THEO)  Long-Acting inhaled β 2-Agonists (LABA)  Systemic GlucoCorticoSteroids (SGCS) 6

7. 7 Pharmacologic Therapy (Staging) Routine Monitoring (Symptoms & Lung Function) Prevention (Trigger factors co- morbid conditions) Patient education (create a partnership Between Clinician & patient) Successful Asthma Management

8. 8 Pharmacologic Therapy (Staging) Routine Monitoring (Symptoms & Lung Function) Prevention (Trigger factors co- morbid conditions) Patient education (create a partnership Between Clinician & patient) Successful Asthma Management

9. 9 Initial Evaluation to classify Asthma Severity Treating for 4-6 weeks to achieve control Total evaluation after treatment to identify the Level of Control Treatment Modification : Step up or Step down

10. Initial Evaluation to classify Asthma Severity 10

11. Assessment of asthma severity using symptoms and PEF in patients presenting for the First Time on No Treatment 11 Old calcification

12. Classification of Severity 12

13. 13 CLASSIFY SEVERITY Clinical Features Before Treatment Symptoms NocturnalSymptoms FEV 1 or PEF STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Intermittent Continuous Limited physical activity Daily Attacks affect activity > 1 time a week but 1 time a week but < 1 time a day < 1 time a week Asymptomatic and normal PEF between attacks Frequent > 1 time week > 2 times a month 2 times a month 2 times a month 60% predicted Variability > 30% 60 - 80% predicted Variability > 30%  80% predicted Variability 20 - 30% 80% predicted Variability < 20%

14. Treating for 4-6 weeks to achieve control 14

15. Asthma Education Environmental Control As needed rapid-acting inhaled B2-agonist 15 TREATMENT STEPS REDUCEINCREASE STEP 1 STEP 2 STEP 3 STEP 4 STEP 5

16. 16 REDUCEINCREASE Treatment steps Step 1 Step 2 Step 3 Step 4 Step 5 Asthma education Environmental control As-needed rapid-acting B2- agonist Controller options Select one Add one or more Add one or both Low-dose inhaled ICS Leukotriene modifier Low-dose ICS plus long-acting B2-agonist Low-dose ICS plus long-acting B2-agonist Medium-or high-dose ICS Low-dose ICS plus leukotriene modifier Low-dose ICS plus sustained release theophylline Medium-or high- dose ICS plus long-acting B2- agonist Leukotrien e modifier Sustained release theophylline Oral glucocorticoste roid (lowest dose) Anti-IgE treatment

17. REDUCEINCREASE Asthma education Environmental control As-needed rapid-acting  2 -agonist Controller options Select one Add one or moreAdd one or both Low-dose inhaled ICS Low-dose ICS plus long-acting  2 -agonist Medium-or high-dose ICS plus long-acting  2 - agonist Oral glucocorticosteroid (lowest dose) Leukotriene modifier Medium-or high-dose ICS Leukotriene modifierAnti-IgE treatment Low-dose ICS plus leukotriene modifier Sustained release theophylline Low-dose ICS plus sustained release theophylline Treatment steps Step 1 Step 2 Step 3 Step 4 Step 5

18. As needed Short-acting inhaled B2-agonist (SABA) Indicated in all age groups18

19. 19 Low-dose ICS Montelukast Preferred Alternative

20. 20 Low-dose ICS LABA Montelukast SR-Theo Or Preferred + +

21. OR21 Medium- dose ICS High – dose ICS

22. children 0- 4 years of age22 Medium-dose ICS

23. 23 Medium -dose ICS plus LABA High-dose ICS plus LABA Montelukast SR-Theo +/-

24. Step 4 Moderate & Severe Asthma children 0- 4 years of age children 0- 4 years of age 24 Medium-dose ICS Montelukast +

25. 25 Medium dose ICS plus LABA Montelukast SR-Theo +/- Oral Glucocorticosteroids low dose Anti-IgE High-dose ICS plus LABA + +

26. Total evaluation after treatment to identify the Level of Control 26

27. 27 Total Asthma control Normal Lung Function Better Quality of life Non Exacerbation

28. 28 Better Quality of life

29. 29

30. 30

31. 31

32. 32

33. 33 Levels of Asthma Control

34. Characteristic Controlled (All of the following) Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week 3 or more features of partly controlled asthma present in any week Limitations of activities NoneAny Nocturnal symptoms / awakening NoneAny Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day ExacerbationNoneOne or more / year1 in any week

35. 35 Treatment Modification : Step up or Step down Step up or Step down

36. 36 Step up after 4-6 weeks Of Treatment Step up after 4-6 weeks Of Treatment Step down After 3-6 months of Treatment Step down After 3-6 months of Treatment STEP 1 STEP 2 STEP 3 STEP 4 STEP 5

37. Controlled Partly controlled Uncontrolled Exacerbation LEVEL OF CONTROL Maintain and find lowest controlling step Consider stepping up to gain control Step up until controlled Treat as exacerbation TREATMENT ACTION Treatment steps Step 1 Step 2 Step 3 Step 4 Step 5 REDUCEINCREASE

38. Stepping Down Treatment When Asthma Is Controlled

39. Regular use of treatment in practice: stepping down Low-dose ICS plus sustained release theophylline Sustained release theophylline Low-dose ICS plus leukotriene modifier Anti-IgE treatmentLeukotriene modifier Medium-or high-dose ICS Leukotriene modifier Oral glucocorticosteroid (lowest dose) Medium-or high-dose ICS plus long-acting  2 - agonist Low-dose ICS plus long-acting  2 -agonist Low-dose inhaled ICS Controller options Add one or bothAdd one or moreSelect one Treatment steps Step 1 Step 2 Step 3 Step 4 Step 5

40. LABA + ICS (M) LABA + ICS (L) Stop LABA / ICS (L) once daily LABA + ICS (H)

41. Controllers + ICS (M) Controllers + ICS (L) Stop Controllers / ICS (L) once daily Controllers (Leukotriene modifier or SR Theophylline) ICS ( H ) + +

42. Medications Airway Inflammation ICS Systemic Steroids Leukotriene modifiers Cromolyn and nedocromil Airway Obstruction LABASABA AnticholinergicTheophylline Airway Remodelling ICS

43. Corticosteroids Corticosteroids are the most useful antiinflammatory agents

44. Corticosteroids are available for Oral Parenteral and inhaled use

45. Inhaled gluCocorticoSteroids ( ICS ) Inhaled glucocorticosteroids are the most effective controller therapy in all ages Evidence A in Long Term asthma Management

46. ICS are safe and effective treatment for moderate- to- severe asthma The longterm use of ICS has been associated with a good safety profile

47. Side Effects High doses ICS (eg, 1,000 μg/d) Hypophyseal Pituitary adrenal axis suppression can usually be avoided by the use of a spacer or holding chamber and by rinsing the mouth after each use Local adverse effects Hoarseness Dysphonia Cough oral candidiasis

48. Oral preparations (prednisone) are useful for the treatment of acute exacerbations of asthma that are unresponsive to bronchodilator therapy Doses of 40 to 60 mg/d are administered until the patient responds and then the dosage can be slowly tapered down

49. IV corticosteroids (methylprednisolone, 60 to 80 mg every 6 to 8 h for 1 or 2 days) preventing further progression of the severe asthma exacerbation That requires hospitalization

50. Side Effects Osteoporosis Cataractsdiabetes mellitus depression of immunity to infection

51. Leukotriene Modifiers ( LM ) LT pathway modifiers (LPMs) are also medications that are considered to be asthma controllers Evidence A in Long Term asthma Management

52. These agents have been shown to be effective in preventing allergic rhinitis

53. Prevention of exercise - induced bronchospasm Adolescents 15 years and Adults: 10 mg at least 2 hours prior to exercise Additional doses should not be administered within 24 hours Adolescents 15 years and Adults: 10 mg at least 2 hours prior to exercise Additional doses should not be administered within 24 hours

54. Montelukast DOSING 6 months to 5 years4 mg/day6-14 years5 mg/day Adolescents >14 years and Adults 10 mg/day

55. Short - Acting inhaled β 2- Agonists ( SABA ) Evidence A Relief bronchospasm during acute exacerbations of asthma Pretreatment of exercise-induced bronchoconstriction

56. Short - Acting inhaled β 2- Agonists ( SABA ) Treatment should be taken as needed in controlled asthma Regular SABA Increased risk of: Exacerbation Hospital admission in children

57. Short - Acting inhaled β 2- Agonists ( SABA ) The need for regularly scheduled doses of SABAs should alert the physician to the need for more intense antiinflammatory medication

58. Long - Acting inhaled β 2- Agonists ( LABA ) Evidence A in Long Term asthma Management in children, adolescents and adults: Control of chronic symptoms Prevent nocturnal symptoms Exercise-induced bronchoconstriction

59. Long - Acting inhaled β 2- Agonists ( LABA ) The effect of (LABA) has not yet been adequately studied in infants 5 years and younger

60. Long-Acting inhaled β2-Agonists LABASalmeterol > 4 years old Inhalation 50 mcg / 12 hours Formoterol > 5 years old Inhalation 12 mcg / 12 hours

61. Formoterol (Pharmacodynamics) Onset Within 3 minutes Peak effect 80% of peak effect within 15 minutes Duration Improvement in FEV1 observed for 12 hours in most patients

62. ombination Strategy Rational Better control Better lung function Better QOL Synergy ICS + LABA

63. Anticholinergics produce bronchodilatation by reducing vagal tone

64. Anticholinergics In Acute Asthma Reliever medication but less effective than SABA substitute bronchodilator when side effects preclude the use of β2-agonist Not recommended for long-term management of asthma in children

65. Anticholinergics The combination between SABA & Anticholinergics Significant Improvement in pulmonary function Significantly reduces the risk of hospital admission

66. Medications Airway Inflammation ICS Systemic Steroids Leukotriene modifiers Cromolyn and nedocromil Airway Obstruction LABASABA AnticholinergicTheophylline Airway Remodelling ICS

67. Theophylline Theophylline is an effective bronchodilator and has antiinflammatory properties Evidence B in Long Term asthma Management in children, adolescents and adults

68. Theophylline The side effects are more pronounced 8 to 15 μg/Ml therapeutic 20 to 30 μg/mL GI side effects blood levels in excess of this range Serious cardiac arrhythmias and seizures

69. Anti-IgE therapy in Allergic Diseases

70. Omalizumab Xolair® is a: IgG monoclonal antibody (recombinant DNA-derived) IMMUNOMODULATORY AGENTS (Anti IgE )

71. Anti IgE inhibits the binding of IgE to mast cells by forming complexes with circulating free IgE down-regulation of basophil and mast-cell receptors and the subsequent release of inflammatory mediators IMMUNOMODULATORY AGENTS (Anti IgE )

72. Xolair® FDA approved for subcutaneous use in severe asthmatics incomplete symptom control with inhaled corticosteroid treatment

73. Subcutaneous injection under medical supervision 150 mg – 375 mg every 2- 4 weeks Subcutaneous injection under medical supervision 150 mg – 375 mg every 2- 4 weeks

74. Side Effects one in 1000 patients Anaphylaxis 1 % of patients urticarial skin rash occur in 44 % Mild injection site reactions

75. ANTI - IgE THERAPY IN OTHER DISEASES Allergic Rhinitis Atopic Dermatitis Food Allergy Chronic Urticaria Churg-strauss Syndrome Allergic Rhinitis Atopic Dermatitis Food Allergy Chronic Urticaria Churg-strauss Syndrome

76. Important limits of clinical use Individuals must be 12 years of age or older

77.  Exacerbations   Symptoms   On-demand medication   Steroid-sparing  Quality of life   Lung function (  )  Side effects  Omalizumab in allergic asthma